The in vivo delivery of therapeutic agents within the body of a patient is common in the practice of modern medicine. In vivo delivery of therapeutic agents is often implemented using medical devices that may be temporarily or permanently placed at a target site within the body. These medical devices can be maintained, as required, at their target sites for short or prolonged periods of time, delivering biologically active agents at the target site.
In accordance with certain delivery strategies, a therapeutic agent is provided within or beneath a biostable polymeric layer that is associated with a medical device. Once the medical device is placed at the desired location within a patient, the therapeutic agent is released from the medical device with a profile that is dependent, for example, upon the nature of the therapeutic agent and of the polymeric layer, among other factors.
Examples of such devices include drug eluting coronary stents, which are commercially available from Boston Scientific Corp. (TAXUS), Johnson & Johnson (CYPHER), and others. For example, the TAXUS stent contains a non-porous polymeric coating consisting of an antiproliferative drug (paclitaxel) within a biostable polymer matrix. The drug diffuses out of the coating over time. Due to the relatively low permeability of paclitaxel within the polymer matrix and due to the fact that the polymer matrix is biostable, a residual amount of the drug remains in the device beyond its period of usefulness (e.g., after the coating is overgrown with cells). Moreover, smooth surfaces by their nature do not allow for cell in-growth. Furthermore, smooth surfaces commonly exhibit inferior cell adhesion and growth relative to textured surfaces. For example, feature sizes less than 100 nm are believed to promote adhesion of proteins such as fibronectin, laminin, and/or vitronectin to the surface, and to provide a conformation for these proteins that better exposes amino acid sequences such as RGD and YGSIR which enhance endothelial cell binding. See, e.g., Standard handbook of biomedical engineering and design, Myer Kutz, Ed., 2003 ISBN 0-07-135637-1, p. 16.13. Moreover, small surface features are associated with an increase in surface energy, which is believed to increases cell adhesion. See, e.g., J. Y. Lim et al., J. Biomed Mater. Res. (2004) 68A(3): 504-512. In this regard, submicron topography, including pores, fibers, and elevations in the sub-100 nm range, has been observed for the basement membrane of the aortic valve endothelium as well as for other basement membrane materials. See R. G. Flemming et al., Biomaterials 20 (1999) 573-588, S. Brody et al., Tissue Eng. 2006 Feb; 12(2): 413-421, and S. L. Goodman et al., Biomaterials 1996; 17: 2087-95. Goodman et al. employed polymer casting to replicate the topographical features of the subendothelial extracellular matrix surface of denuded and distended blood vessels, and they found that endothelial cells grown on such materials spread faster and appeared more like cells in their native arteries than did cells grown on untextured surfaces. See also F. L. Yap et al., “Protein and cell micropatterning and its integration with micro/nanoparticles assembly,” Biosensors and Bioelectronics 22 (2007) 775-778.